Genel Ferah, Unal Faith, Ozgenc Funda, Aksu Guzide, Aydogdu Sema, Kutukculer Necil, Yagci Rasit V
Department of Pediatrics, Faculty of Medicine, Ege University, Bornova, Izmir, Turkey.
J Gastroenterol Hepatol. 2003 Jun;18(6):645-50. doi: 10.1046/j.1440-1746.2003.03050.x.
In the development of chronic hepatitis with hepatitis B virus infection and in response to therapy, the immune status of the infected host plays a critical role. In this study, immunological variables were assessed in patients before interferon alpha and lamivudine therapy to determine if any pretreatment immunological parameter could be an indicator of response to therapy in childhood chronic hepatitis B infection.
Forty-four patients with chronic hepatitis B virus infection, aged 9.0 +/- 3.9 years, were enrolled in the study. The pretreatment clinical features, biochemical test results, histological activity indexes and immunological parameters were evaluated. All patients received interferon alpha for 6 months and lamivudine for 52 weeks. Four patients who could not be followed up were excluded from the study. The other 40 patients have been followed for a mean period of 27.5 +/- 9.7 months after therapy discontinuation.
Seventeen patients showed loss of hepatitis B early antigen (HBeAg) with appearance of anti-HBe (42.5%) and six of those who responded also showed loss of hepatitis B surface antigen (HBsAg) with the presence of anti-HBs (15%). Except elevated aspartate aminotransferase levels, there was no significantly correlation between response and sex, age, pretreatment duration of disease and histological activity indexes. Pretreatment immunoglobulins (Ig), IgG subclasses, complement C3, C4 and secretory IgA levels were also not found to be significantly related to response. The evaluation of lymphocyte subsets showed that therapy responders had significantly reduced pretreatment ratios of CD4/CD8+ lymphocytes due to prominent increased percentages of CD8+ cells. The other cellular immunity parameters and some cell surface adhesion molecules were similar in both groups.
This study emphasizes the importance of increased pretreatment CD8+ lymphocyte percentages leading to a significant decrease in CD4/CD8 ratio in chronic hepatitis B virus infection of childhood as an immunological factor predicting response to treatment.
在乙型肝炎病毒感染所致慢性肝炎的发展过程以及对治疗的反应中，受感染宿主的免疫状态起着关键作用。在本研究中，对患者在接受α干扰素和拉米夫定治疗前的免疫变量进行评估，以确定在儿童慢性乙型肝炎感染中，任何治疗前免疫参数是否可作为治疗反应的指标。
44例慢性乙型肝炎病毒感染患者，年龄9.0±3.9岁，纳入本研究。对治疗前的临床特征、生化检测结果、组织学活性指数和免疫参数进行评估。所有患者接受α干扰素治疗6个月和拉米夫定治疗52周。4例无法随访的患者被排除在研究之外。其余40例患者在停药后平均随访27.5±9.7个月。
17例患者出现乙肝e抗原（HBeAg）消失并出现抗-HBe（42.5%），其中6例有反应者还出现乙肝表面抗原（HBsAg）消失并出现抗-HBs（15%）。除天冬氨酸转氨酶水平升高外，反应与性别、年龄、治疗前病程和组织学活性指数之间无显著相关性。治疗前免疫球蛋白（Ig）、IgG亚类、补体C3、C4和分泌型IgA水平也与反应无显著相关性。淋巴细胞亚群评估显示，由于CD8+细胞百分比显著增加，治疗反应者治疗前CD4/CD8+淋巴细胞比值显著降低。两组的其他细胞免疫参数和一些细胞表面黏附分子相似。
本研究强调了在儿童慢性乙型肝炎病毒感染中，治疗前CD8+淋巴细胞百分比增加导致CD4/CD8比值显著降低作为预测治疗反应的免疫因素的重要性。
